In Utero Glossoptosis in Fetuses With Robin Sequence: Measurements From Prenatal MRI.
Glossoptosis causes airway obstruction in patients with Robin sequence (RS), but little is known about the in-utero tongue. The purpose of this study was to assess shape and position of the fetal tongue on prenatal magnetic resonance imaging (MRI) to determine if this is predictive of postnatal RS. Retrospective case-control study including fetuses with prenatal MRIs performed from 2002 to 2017. Inclusion criteria were (1) prenatal MRI of adequate quality, (2) live born and evaluated postnatally for craniofacial findings. Subjects were divided into groups based on postnatal findings: (1) RS, (2) micrognathia without RS, and (3) a gestational-age-matched control group with normal craniofacial morphology. Outcome variables were based on the prenatal MRI and included fetal tongue height, length, and width, tongue shape index (TSI, ratio of height to length), and observation of tongue touching the posterior pharyngeal wall. A total of 116 subjects with mean gestational age at MRI of 25.6 ± 5.1 weeks were included: RS, n = 27 (23%); micrognathia, n = 35 (30%); control, n = 54 (47%). Tongue length was significantly shorter ( P = .009) and TSI was significantly larger in the RS group ( P < .0001). The tongue touched the posterior pharyngeal wall in 5 (19%) of the RS group and in no subjects in the other groups ( P < .0001). In utero tongue shape and position were significantly different in fetuses with postnatal RS compared to those with isolated micrognathia and controls. Prenatal MRI tongue characteristics may be predictors for postnatal RS.


Magnetic phase diagram of clathrate compound Ce3Pd20Si6 with quadrupolar ordering.
We present results of specific heat measurements on a Ce3Pd20Si6 single crystal and construct the magnetic phase diagram for the three cubic principal directions [100], [110] and [111]. The highly anisotropic phase diagram is discussed and can be qualitatively explained by the Zeeman splitting at the 8c-site. For B ‖ [100], the present study found two different quadrupolar ordered phases, which meet the paramagnetic phase at a tri-critical point and establish the new phase boundaries.


Digital subtraction angiography of the thoracic aorta.
Forty-three patients with acquired and congenital abnormalities of the thoracic aorta were studied using digital subtraction angiography (DSA) after an intravenous bolus injection of 40 ml of contrast material. Abnormalities studied included coarctation, pseudocoarctation, Marfan syndrome, cervical aorta, double aortic arch, aneurysm, dissection, and tumor. Twenty-four patients also had conventional angiography. DSA was accurate in 95% of cases; in the other 5%, involving patients with acute type I dissection, the coronary arteries could not be seen. The authors concluded that in 92% of their patients, DSA could have replaced the standard aortogram.


Carcinoma of the lung. Who will benefit from surgery?
The present staging methods for non-small-cell lung cancer provide little more than epidemiologic assessment of prognosis for grossly defined groups of patients. Except in extreme instances, physicians can tell patients very little about their prognosis or the need for supplemental therapy. More effective and less toxic chemotherapeutic agents are needed to treat this disease. Although improved results have been attained with combination therapy in patients with good functional status and less advanced disease, little help is available for lung cancer patients with advanced disease. Treating this large group of patients remains a great challenge for the surgical and medical oncologist.


Remotely Controlled Mandibular Positioning During Drug-Induced Sleep Endoscopy Toward Mandibular Advancement Device Therapy: Feasibility and Protocol.
The potential of a remotely controlled mandibular positioner (RCMP) during sleep studies in individual patients suffering from obstructive sleep apnea (OSA) for the determination of the effective target protrusive position (ETPP) of the mandible has been demonstrated. The research goal of this study was to assess the feasibility of the application of RCMP during drug-induced sleep endoscopy (DISE) for the determination of ETPP. Ten patients in whom OSA was diagnosed (50% male; age 54 ± 9.5 years; body mass index 26.9 ± 2.1 kg/m2; apnea-hypopnea index 28.4 ± 13.2 events/h) were enrolled prospectively. Dental RCMP trays were fitted during wakefulness. Maximal protrusion and edge-to-edge positions were measured. Upper airway collapsibility was scored during DISE, including full-range mandibular RCMP titration within 45 minutes. ETPP was defined as the mandibular threshold protrusion yielding a stable upper airway in the absence of snoring, oxygen desaturation and apneas. RCMP trays were retentive and no adverse reactions occurred. RCMP was fitted intraorally prior to sedation with maxillary and mandibular trays in edge-to-edge position. Upon sedation, progressive protrusion was performed followed by reversed titration until ETPP was noted. In one patient ETPP was not within the mandibular range of motion. In one patient RCMP needed to be removed because of clenching. The results of this study illustrate that it is feasible to use RCMP during DISE and to determine ETPP within 45 minutes. Comparative research with polysomnography would be useful to further validate the therapy outcome upon use of RCMP during DISE.


[The need for psychotherapy in school-age children].
The article reports the results of an investigation of N = 1.969 school children (aged 6 to 17) of three rural communities, who had been assessed by a German version of the Child Behavior Checklist (Achenbach u. Edelbrock 1983). It was intended to determine the prevalence of clinical maladjustment and to investigate the effectiveness of selective factors in referring to child psychiatric facilities. The case definition was based on those items (behavior disorders), which were rated as in need for counseling or treatment by experts. After a statistical comparison with a sample of referred children the criterion was set up at two or more of such critical items. 12.7% of the school children fulfilled this condition, but most of them (87.6%) had not used institutional services. The rate of children and adolescents, who need psychotherapy was estimated lower (less than 10%). The readiness to refer clinical maladjusted children to child psychiatric facilities was influenced by age and socio economic status, but not by sex and foreign nationality.


Mutants of Streptomyces cattleya defective in the synthesis of a factor required for thienamycin production.
Thienamycin non-producing mutants of Streptomydes cattleya were identified that displayed a cross-feeding relationship. A diffusible product from one of these mutants (RK-11) resulted in restoration of thienamycin production when fed to cultures of another mutant (RK-4). In vivo radiolabeling experiments were conducted to test whether the RK-11 mutant produced a late biosynthetic intermediate which contained a carbapenem ring and a cysteaminyl and/or a hydroxyethyl side chain. Both [35S]cystine and [methyl-3H]methionine were used to label the RK-11 product which was then fed to RK-4 cultures. None of the thienamycin subsequently produced by RK-4 converter cells was labeled, implying the lack of either side chain of the thienamycin molecule in the RK-11 product. Further stability studies suggested that the RK-11 product does not contain a carbapenem ring. Additional feeding experiments with RK-4 cells also ruled out the possibility that the RK-11 product is a co-factor necessary for thienamycin production. It is concluded that the RK-11 product may regulate expression of the thienamycin gene cluster.


High-volume hemofiltration reduces short-term mortality with no influence on the incidence of MODS, hospital stay, and hospitalization cost in patients with severe-acute pancreatitis: A meta-analysis.
This study aimed to investigate the efficiency, safety and cost-efficiency of blood purification (BP) in treating patients with severe-acute pancreatitis (SAP). A literature search was conducted using PubMed, OVID, International Clinical Trials Register (ICTRP), and Cochrane Central Register of Controlled Trials (CENTRAL). A total of 11 prospective studies and 6 retrospective studies, which reported the mortality of 1279 SAP patients, were included for analysis. Decreased short-term mortality and incidence rate of infection were observed in the high-volume hemofiltration (HVHF) group, but not in patients treated with other types of BP. There was no significant difference in the incidence of multiple-organ dysfunction (MODS), duration of hospital stay, or cost of hospitalization between the BP and non-BP groups. The starting time point, substitution fluid flow rate, filter membrane type, hemofilter change interval, anticoagulation, and sustaining times of BP varied across studies. In conclusion, HVHF may reduce the short-term mortality (<4 weeks), not long-term mortality, of SAP patients by decreasing the incidence of infection, while other types of BP did not show a significant beneficial effect. Neither HVHF nor other BP patterns affect the duration of hospital stay, cost of hospitalization, or incidence of MODS in SAP patients.


Enabling simultaneous valorization of tannery effluent and waste plastic via sustainable preparation of Cr-BDC MOFs for water adsorption.
Advanced materials undergo a complex and lengthy process of maturation for scaling up and deployment, mainly due to the high cost of their precursors. Therefore, it is highly desirable to fabricate highly valuable advanced porous solid-state materials, with proven applicability, by sustainably combining organic and inorganic waste materials as precursors. This study successfully demonstrates the preparation of Cr-terephthalate Metal-Organic Frameworks (Cr-BDC MOFs) by combining metal salt and organic linker extracted from tannery effluent and waste plastic bottles. The waste from tanneries was used as the source of Cr(III), while terephthalic acid was obtained from the alkaline hydrolysis of plastic bottles. Appropriate extraction and assembly processes led to the functional Cr-BDC MOFs, MIL-101(Cr) and MIL-53(Cr). The prepared MOFs showed similar properties (surface area, hydrolytic and thermal stability, and water adsorption performance) to similar MOFs synthesized from pure commercial-grade precursors, as confirmed by N2 sorption, XRD, TGA, and water adsorption experiments. The advancements made in this study represent significant progress in overcoming the bottleneck of MOF production cost efficiency via applying sustainability principles and pave the way for easy scaling-up and maturation of MOF-based processes, for air dehumidification and water harvesting as a case study.


(19) F NMR Spectroscopy as a Highly Sensitive Method for the Direct Monitoring of Confined Crystallization within Nanoporous Materials.
The introduction of fluorine into the structure of pharmaceuticals has been an effective strategy for tuning their pharmacodynamic properties, with more than 40 new drugs entering the market in the last 15 years. In this context, (19) F NMR spectroscopy can be viewed as a useful method for investigating the host-guest chemistry of pharmaceuticals in nanosized drug-delivery systems. Although the interest in confined crystallization, nanosized devices, and porous catalysts is gradually increasing, understanding of the complex phase behavior of organic molecules confined within nanochambers or nanoreactors is still lacking. Using (19) F magic-angle-spinning NMR spectroscopy, we obtained detailed mechanistic insight into the crystallization of flufenamic acid (FFA) in a confined environment of mesoporous silica materials with different pore diameters (3.2-29 nm), providing direct experimental evidence for the formation of a molecular-liquid-like layer besides crystalline confined FFA form I.


Empyema Thoracis in Children: A 5-Year Experience in a Tertiary Care Institute.
Empyema thoracis (ET) in children is a disease of significant morbidity and mortality. In the event of failure to resolute following intercostal chest tube drainage (ICD), thoracotomy decortication (TDC) remains the treatment of choice. We have reviewed the outcome of management of 96 cases of ET with the intent to establish the scope of ICD as primary form of the management. This is a retrospective study of 96 patients of ET who were managed in pediatric surgery department over a period of 5 years (April 2013 - March 2018). Ninety-six patients at a single center met inclusion criteria for having ET and underwent ICD. We excluded the cases where video-assisted thoracoscopic surgery was provided as primary treatment. The patients were categorized into complicated and uncomplicated groups. Those with pyopneumothorax, encysted empyema, multiloculated empyema, and bilateral ET were assigned as complicated group. There were two treatment groups: (I) those responded with ICD alone (II) those with ICD followed by TDC. All 96 cases received ICD as primary management. There were 54 uncomplicated cases and 42 complicated cases. Out of 42 complicated cases, 26 patients recovered with ICD alone and 16 patients needed TDC. A total of 80 (83.33%) patients (54 uncomplicated ± 26 complicated) recovered with ICD alone. Significant complications were encountered in follow-up of patients who underwent delayed thoracotomy in the form of overriding of the ribs (n = 3) and postoperative air leak (n = 4). There was no mortality in our series. Early initiation of management of ET with intercostal tube drainage is simple, safe, effective even in complicated cases, and has less complications. Thoracotomy with decortication should be reserved for ICD failure cases.


Epilogue: Implementation Science in CSD and Starting Where You Are.
In this epilogue for the Clinicians and Researchers Navigating Implementation Science in CSD forum, we begin by summarizing the eight articles in this forum that describe where the field is in terms of published implementation science (IS) articles in communication sciences and disorders (CSD) and how numerous teams have begun incorporating IS into their research programs. We then situate these articles across three themes: (1) levels of analysis and support; (2) research methods, frameworks, and models; and (3) underserved populations. Next, we consider the challenges and opportunities for conducting IS in CSD. Finally, we conclude by offering tangible steps for researchers, department heads, clinicians, patients, organizations/administrators, and funders in doing and supporting IS research in CSD.


The origin and evolution of human ampliconic gene families and ampliconic structure.
Out of the nine male-specific gene families in the human Y chromosome amplicons, we investigate the origin and evolution of seven families for which gametologous and orthologous sequences are available. Proto-X/Y gene pairs in the original mammalian sex chromosomes played major roles in origins and gave rise to five gene families: XKRY, VCY, HSFY, RBMY, and TSPY. The divergence times between gametologous X- and Y-linked copies in these families are well correlated with the former X-chromosomal locations. The CDY and DAZ families originated exceptionally by retroposition and transposition of autosomal copies, respectively, but CDY possesses an X-linked copy of enigmatic origin. We also investigate the evolutionary relatedness among Y-linked copies of a gene family in light of their ampliconic locations (palindromes, inverted repeats, and the TSPY array). Although any pair of copies located at the same arm positions within a palindrome is identical or nearly so by frequent gene conversion, copies located at different arm positions are distinctively different. Since these and other distinct copies in various gene families were amplified almost simultaneously in the stem lineage of Catarrhini, we take these simultaneous amplifications as evidence for the elaborate formation of Y ampliconic structure. Curiously, some copies in a gene family located at different palindromes exhibit high sequence similarity, and in most cases, such similarity greatly extends to repeat units that harbor these copies. It appears that such palindromic repeat units have evolved by and large en bloc, but they have undergone frequent exchanges between palindromes.


Canine salivary gland carcinoma treated with stereotactic body radiation therapy: a retrospective case series.
The aim of this study was to describe the therapeutic outcomes of dogs with locally advanced salivary gland carcinomas (SGC) following stereotactic body radiation therapy (SBRT). A single institution retrospective study was conducted of client-owned dogs with macroscopic SGC treated with SBRT. Patient signalment, clinical characteristics, and treatment parameters were recorded. Clinical benefit was determined based on follow-up physical examination and medical history. Progression-free interval (PFI), median survival time (MST), and disease-specific survival (DSS) were calculated using Kaplan-Meier analysis. Acute and late toxicity were recorded according to Veterinary Radiation Therapy Oncology Group (VRTOG) criteria. Six patients were included in the study. Tumor origins were mandibular (n = 3), parotid (n = 2), and zygomatic (n = 1) salivary glands. The SBRT prescription was 10 Gy × 3 daily or every other day. All patients (100%) experienced clinical benefit from treatment at a median time of 34 days (range 28-214). No local or regional nodal failure was reported following SBRT. Progressive pulmonary metastatic disease was documented in three dogs (50%). The median PFI was 260 days (range 43-1,014) and the MST was 397 days (range 185-1,014). Median DSS was 636 days (range 185-1,014). Four dogs (66.6%) died of confirmed or suspected metastatic SGC. The reported acute side effects included grade 2 mucositis (n = 1) and vision loss (n = 1). No late side effects were recorded. This study suggests that SBRT may provide durable local control for invasive SGC in dogs. Further investigation in a larger cohort of patients is warranted. The incidence of reported acute and late toxicity was low.


Results of a community thyroid screening program: who will benefit?
To describe the results of a community-based thyroid screening program. We review the recruitment process, the screening questionnaire, the laboratory procedure, and the data analysis. News media advertisements and facility-sponsored communications were used to recruit 1,176 participants, each of whom completed a health questionnaire and had blood withdrawn for a thyroid-stimulating hormone (TSH) assay. Most participants were female (78%), Caucasian (92%), and age 50 years or older (61%). Data from 1,139 participants were analyzed. Abnormal TSH values were found in 107 participants: TSH was low in 21 (2%) and elevated in 86 (8%). Elevated TSH values occurred in 8% of females, 7% of males, 8% of Caucasians, and 7% of Hispanics. Although the percentage of elevated TSH values tended to increase with advancing age, primarily in females, 5% of participants younger than 50 years of age had an elevated TSH. No associations were apparent between abnormal TSH values and health maintenance organization membership, self-rating of overall health, or presence of thyroid-related symptoms. Participants who rated their overall health as "excellent" or "very good" accounted for 48% of the TSH values >12 microIU/mL. Experience gained from the conduct of this screening program may help shape the expectations of future screening programs that use disease awareness and self-motivation and provide insights into program design that may maximize participation by the desired target audiences.


The Relationship between Polyneuropathy and Cognitive Functions in Type 2 Diabetes Mellitus Patients.
Type 2 Diabetes Mellitus (DM) is a risk factor for mild cognitive impairment (MCI), Alzheimer's disease and vascular dementia. However, it is not known which pathophysiological mechanisms lead to impairment in cognitive functions in Type 2 DM. This study aims to compare the cognitive functions of diabetic patients with and without polyneuropathy using standardized Mini-Mental Test (MMSE) and the Montreal Cognitive Assessment Scale (MoCA) and to assess whether the presence of polyneuropathy is a predictive factor for the development of cognitive impairment. Patients with DM who underwent our EMG laboratory for polyneuropathy between January 2014 and January 2015 were included in this study. Patients who underwent electrophysiological examinations were evaluated for polyneuropathy. Patients with polyneuropathy were classified as a patient group and other patients as a control group. In all cases, MMSE and MoCA were administered. The demographic data and educational status of the patients were recorded. Hypertension, coronary artery disease, smoking and alcohol use were questioned. Their complaints, duration of illness and the treatment they were receiving were questioned. Glycosylated hemoglobin (HBA1C) values in the last three months and physical examination findings of patients were recorded. Patients with and without polyneuropathy were compared with statistical methods. Polyneuropathy was detected in 34 (42%) of the 81 patients who participated in our study. The age, disease duration and HBA1C levels were statistically higher in the polyneuropathy group than in the control group (p=0.024, p=0.000, p=0.016). However, there was no statistically significant difference between MMSE and MoCA scores of these groups. In both groups, there were no patients scoring below the MMSE cut-off value of 24. Seventeen of the 34 patients (50%) in the polyneuropathic group and 19 (40,4%) of the 47 patients in the control group had scores below the MoCA cut-off value 21. However, there was no statistically significant difference between the two groups. We also found that the mean MoCA value of all DM patients was 21, which was the MoCA cut-off value. Also, factors affecting cognitive functions in all Type 2 DM patients were evaluated by logistic regression analysis, and it was found that duration of education was an independent factor affecting cognitive impairment (OR=8.167; p=0.001). In our study, we did not observe significant differences between MMSE and MoCA scores of Type 2 DM patients with and without polyneuropathy. However, the cross-sectional nature of our study makes it impossible to comment on this issue. To clarify whether the presence of polyneuropathy is a predictive factor in the development of cognitive impairment in Type 2 DM, there is a need for a larger sample group and long-term follow-up studies. It has also been shown that patients with Type 2 DM may have low scores according to the MOBID cut-off value even though peripheral neurologic involvement findings are not observed. In the Type 2 DM population, it has also been shown that MoCA may be affected by education level.


Famciclovir: a new systemic antiviral agent for herpesvirus infections.
Acyclovir was the first antiviral drug approved for the treatment of herpes zoster. Several new antiviral agents have since been introduced, one of which is famciclovir. The pharmacokinetics of famciclovir allow a more convenient dosing schedule than the schedule used with acyclovir. Famciclovir is metabolized in the liver, but the P450 cytochrome system is not involved. Both acyclovir and famciclovir accelerate cutaneous healing, but studies suggest that famciclovir may reduce the severity of postherpetic neuralgia when compared with placebo. Famciclovir is currently approved only for use in immunocompetent patients, but clinical trials involving immunocompromised patients are in progress.


Differential regulation of Th1-type and Th2-type cytokine profiles in pancreatic islets of C57BL/6 and BALB/c mice by multiple low doses of streptozotocin.
In the nonobese diabetic (NOD) mouse, the T helper (Th)1-type inflammatory cytokines interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha play a critical role in the development of type 1 diabetes, whereas the Th2-type anti-inflammatory cytokines interleukin (IL)-4 and IL-10 operate counterregulatory. There are no comprehensive analyses on cytokine profiles in the mouse model of diabetes induced with multiple low doses of streptozotocin (MLD-STZ). Therefore, we used islets to study ex vivo effects of MLD-STZ and in vitro effects of STZ on IFN-gamma, TNF-alpha, IL-4, and IL-10 on both levels of protein-producing cells and the mRNA expression, as well as the mRNA expression of the Th3-type cytokine transforming growth factor TGF-beta1. C57BL/6 and BALB/c mice of both genders were injected intraperitoneally with 40 mg/kg body wt STZ on five consecutive days and islets were isolated on day I and 3 after the fifth STZ-injection. Control mice received the solvent of STZ. In islets of C57BL/6 mice of both genders MLD-STZ similarly stimulated production of IFN-gamma and TNF-alpha, but significantly reduced IL-4 and IL-10 levels in male mice only. Opposite results were obtained in islets of BALB/c mice of both genders. Here, MLD-STZ markedly decreased the levels of IFN-gamma and TNF-alpha, but significantly increased the levels of IL-4 and IL-10. The functional results were in line with MLD-STZ effects on the mRNA expression of the cytokines. Moreover, MLD-STZ effects on the TGF-beta1 mRNA expression were reversed to the effects on IFN-gamma and TNF-alpha. The in vitro effects of STZ in islets, in general, were similar to those exerted by MLD-STZ. Apparently, reduction and upregulation of Th2-type cytokines was more associated with susceptibility and resistance, respectively, to MLD-STZ-induced diabetes than upregulation of Th1-type cytokine levels.


Culture, context and experience in psychiatric diagnosis.
The semiotic theory underlying psychiatric diagnosis views symptoms as more or less direct consequences of psychopathological processes. However, cognitive social psychology and clinical ethnography make it clear that symptom experience is embedded in culturally based systems of meaning and discursive practices. Physiological perturbations are organized, experienced and expressed in terms of a nested series of cognitive schemas involving knowledge about symptoms, illnesses or other models of affliction and broader sociomoral notions of self and personhood. Individuals have many competing schemas at their disposal. The relative prominence or weight given to a specific model is determined by the social context and purposes for which the person is reflecting on, recollecting or recounting their experience. Accounts of symptoms and illness experience are therefore highly dependent on the social context of narration. Psychiatric nosology and the process of clinical assessment must consider the ways in which psychopathology is shaped by social and cultural contexts including those of the family, workplace, and health care system as well as global professional, economic and political interests.


Role of sulfhydryl groups in induction of cell surface down-modulation and shedding of extracellular domain of human TNF receptors in human histiocytic lymphoma U937 cells.
The interaction of different polypeptide growth factors with their cell surface receptors, which are typically rich in cysteine, is modulated by sulfhydryl (SH) reagents. Because the extracellular domain of both human TNFRs are likewise rich in cysteine residues, we examined the effect of SH reagents on these receptors in human histiocytic lymphoma U937 cells, which express both p60 and p80 forms. Iodoacetamide induced down-regulation of cell surface TNFRs in a dose- and time-dependent manner. Down-regulation was complete at 10 mM IAA for 1 h at 37 degrees C. The decrease was minimal at 4 degrees C. The down-modulation was also observed with other cell-permeable and -impermeable thiol reagents. The expression of other cell surface molecules such as CD3, CD11b, CD23, and CD25 were not affected. IAA induced the down-regulation of TNFR on cells of both epithelial and myeloid origin. With the use of receptor-specific Abs, we found that the kinetics of down-modulation of the p60 and p80 receptors by IAA were very similar. We also found that down-modulation was not a result of internalization but rather of the shedding of the receptors, as ascertained by receptor-ligand cross-linking analysis, immunoassay, Western blot analysis, and ligand-blot analysis. When TNFRs with a molecular mass of 80 kDa disappeared from the cell surface, a 42-kDa polypeptide appeared in the medium. Thus, we demonstrate that SH reagents down-regulate TNFRs by inducing shedding of both receptors from the cell surface, most likely by activating an endopeptidase that cleaves the receptor.


Analysis of factors related to browning of red sour soup during fermentation.
As a traditional fermentation food, red sour soup (RSS) is very popular in China. However, browning is always occurred during the process of fermentation, which influences the sensory quality of RSS and limits its further application. Thus, it is meaningful to elucidate the main factors related to browning during the process of fermentation. Herein, the changes in various factors related to browning from group spontaneous (RSS-SF) and inoculant fermentation (RSS-IF) were determined and analyzed. Firstly, the activity changes of enzymes related to browning indicated that browning of group RSS-SF and RSS-IF during fermentation was not related to enzymatic browning. Secondly, path analysis revealed that the main factors related to non-enzymatic browning of group RSS-SF and RSS-IF were oxidation of polyphenol and degradation of ascorbic acid (Vc). The results of this study not only identifies the main factors associate with browning of RSS, but also provides foundation on how to control the browning of RSS in further study.


Effects of client and therapist ethnicity and ethnic matching: a prospective naturalistic study of outpatient mental health treatment in Northern Norway.
We explored the effects of ethnicity on mental health treatment in the population of North Norway that largely consists of indigenous Sami and non-Sami Norwegians. As the two groups are comparable in their socio-economics, ethnic effects can be separated from their most common confounders. The effect of client and therapist ethnicity and client-therapist ethnic match on treatment was examined among psychiatric outpatients in this setting. Client (n=335) and therapist (n=33) demographics and ethnicity were recorded prior to intake. Self-reported psychosocial distress was recorded at intake, termination and 20-month follow-up. Therapists reported their clinical assessment, treatment delivery at intake and discharge. The results indicated that therapist ethnicity was associated with the amount and type of service provided but improvement was not. Both the delivery of treatment and improvement did not differ significantly by client ethnicity. Ethnic matching was associated with greater symptomatic improvement in treatments of moderate duration.


Controls on Methane Occurrences in Aquifers Overlying the Eagle Ford Shale Play, South Texas.
Assessing natural vs. anthropogenic sources of methane in drinking water aquifers is a critical issue in areas of shale oil and gas production. The objective of this study was to determine controls on methane occurrences in aquifers in the Eagle Ford Shale play footprint. A total of 110 water wells were tested for dissolved light alkanes, isotopes of methane, and major ions, mostly in the eastern section of the play. Multiple aquifers were sampled with approximately 47 samples from the Carrizo-Wilcox Aquifer (250-1200 m depth range) and Queen City-Sparta Aquifer (150-900 m depth range) and 63 samples from other shallow aquifers but mostly from the Catahoula Formation (depth <150 m). Besides three shallow wells with unambiguously microbial methane, only deeper wells show significant dissolved methane (22 samples >1 mg/L, 10 samples >10 mg/L). No dissolved methane samples exhibit thermogenic characteristics that would link them unequivocally to oil and gas sourced from the Eagle Ford Shale. In particular, the well water samples contain very little or no ethane and propane (C1/C2+C3 molar ratio >453), unlike what would be expected in an oil province, but they also display relatively heavier δ13 Cmethane (>-55‰) and δDmethane (>-180‰). Samples from the deeper Carrizo and Queen City aquifers are consistent with microbial methane sourced from syndepositional organic matter mixed with thermogenic methane input, most likely originating from deeper oil reservoirs and migrating through fault zones. Active oxidation of methane pushes δ13 Cmethane and δDmethane toward heavier values, whereas the thermogenic gas component is enriched with methane owing to a long migration path resulting in a higher C1/C2+C3 ratio than in the local reservoirs.


Academic, behavioral, and social adaptation of boys with hemophilia/HIV disease.
Examined the intelligence, academic achievement, behavior, and social competency of 37 school-aged boys with hemophilia, 56% with HIV infection. IQ scores fell in the average range, but total reading scores were almost 1 standard deviation below the mean. Parent and teacher ratings of social functioning and behavior fell in the normal range. Absenteeism, an average of 27 days for the previous school year, was inversely correlated with most teacher ratings, indicating that absenteeism may be a significant factor in the academic and social adaptation of children with hemophilia. Overall, boys infected with HIV demonstrated the same level of academic and behavioral adaptation as those uninfected. The need for special education programs and interventions to enhance competency in the school setting is discussed.


Enumerating treelike chemical graphs with given path frequency.
The enumeration of chemical graphs satisfying given constraints is one of the fundamental problems in chemoinformatics. In this paper, we consider the problem of enumerating (i.e., listing) all treelike chemical graphs from a given path frequency. We propose an exact algorithm for enumerating all solutions to this problem on the basis of the branch-and-bound method. To further improve the efficiency of the enumeration, we introduce a new variant of the compound enumeration problem by adding a specification on the number of multiple bonds to the input and design another exact enumeration algorithm. The experimental results show that our algorithms can efficiently solve instances with larger sizes that are impossible to solve by the previous methods. In particular, we apply the latter algorithm to the enumeration problem of the special treelike chemical structures-alkane isomers. The theoretical and experimental results show that our algorithm works at least as fast as the state-of-the-art algorithms specially designed for generating alkane isomers, however using much less memory space.


Estimating the Added Utility of Highly Sensitive Histidine-Rich Protein 2 Detection in Outpatient Clinics in Sub-Saharan Africa.
Most malaria testing is by rapid diagnostic tests (RDTs) that detect Plasmodium falciparum histidine-rich protein 2 (HRP2). Recently, several RDT manufacturers have developed highly sensitive RDTs (hsRDTs), promising a limit of detection (LOD) orders of magnitude lower than conventional RDTs. To model the added utility of hsRDTs, HRP2 concentration in Angolan outpatients was measured quantitatively using an ultrasensitive bead-based assay. The distribution of HRP2 concentration was bimodal in both afebrile and febrile patients. The conventional RDT was able to detect 81% of all HRP2-positive febrile patients and 52-77% of HRP2-positive afebrile patients. The added utility of hsRDTs was estimated to be greater in afebrile patients, where an hsRDT with a LOD of 200 pg/mL would detect an additional 50-60% of HRP2-positive persons compared with a conventional RDT with a LOD of 3,000 pg/mL. In febrile patients, the hsRDT would detect an additional 10-20% of cases. Conventional RDTs already capture the vast majority of symptomatic HRP2-positive individuals, and hsRDTs would have to reach a sufficiently low LOD approaching 200 pg/mL to provide added utility in identifying HRP2-positive, asymptomatic individuals.


Inhibitory effect of modified 5'-capped short RNA fragments on influenza virus RNA polymerase gene expression.
We have shown previously that the 5'-capped short phosphodiester RNA fragments, Cap decoy, (Gm 12 nt) are potent inhibitors of influenza virus RNA polymerase gene expression. Here we investigate the modified capped RNA derivative containing phosphorothioate oligonucleotides (Cap decoy) as a potential influenza virus RNA polymerase inhibitor. The modified 5'-capped short phosphorothioate RNA fragments (Gms 12-15 nt) with the 5'-capped structure (m7GpppGm) were synthesized by T7 RNA polymerase. The 5'-capped short RNA fragments (Gms 12-15 nt) were encapsulated in liposome particulates and tested for their inhibitory effects on influenza virus RNA polymerase gene expression in the clone 76 cells. The 12-15 nt long Gms RNA fragments showed highly inhibitory effects. By contrast, the inhibitory effects of the 13 nt long short RNA fragments (Gm 13 nt) were considerably less in comparison with the 5'-capped short phosphorothioate RNA fragments (Gms 12-15 nt). In particular, the various Gms RNA chain lengths showed no significant differences in the inhibition of influenza virus RNA polymerase gene expression. Furthermore, the capped RNA with a phosphorothioate backbone was resistant to nuclease activity. These phosphorothioate RNA fragments exhibited higher inhibitory activity than the 5'-capped short RNA fragments (Gm 12 nt). These decoys may prove to be useful in anti-influenza virus therapeutics.


Oral immunization with the dodecapeptide repeat of the serine-rich Entamoeba histolytica protein (SREHP) fused to the cholera toxin B subunit induces a mucosal and systemic anti-SREHP antibody response.
The intestinal protozoan parasite Entamoeba histolytica causes amebic dysentery, a major cause of morbidity worldwide. The induction of a mucosal antibody response capable of blocking amebic adhesion to intestinal cells could represent an approach to preventing E. histolytica infection and disease. Here we describe the expression of a chimeric protein containing an immunogenic dodecapeptide derived from the serine-rich E. histolytica protein (SREHP), fused to the cholera toxin B subunit (CtxB). The CtxB-SREHP-12 chimeric protein was purified from Escherichia coli lysates and retained the critical GM1 ganglioside-binding activity of the CtxB moiety. Mice fed the CtxB-SREHP-12 fusion protein along with a subclinical dose of cholera toxin developed mucosal immunoglobulin A and immunoglobulin G and systemic antibody responses that recognized recombinant and native SREHP. Our study confirms the feasibility of inducing mucosal immune responses to immunogenic peptides by their genetic fusion to the CtxB subunit and identifies the CtxB-SREHP-12 chimeric protein as a candidate oral vaccine to prevent E. histolytica infection.


Clustered localization of STAT3 during the cell cycle detected by super-resolution fluorescence microscopy.
Signal transducer and activator of transcription 3 (STAT3) plays a key role in various cellular processes such as cell proliferation, differentiation, apoptosis and immune responses. In particular, STAT3 has emerged as a potential molecular target for cancer therapy. The functional role and standard activation mechanism of STAT3 have been well studied, however, the spatial distribution of STAT3 during the cell cycle is poorly known. Therefore, it is indispensable to study STAT3 spatial arrangement and nuclear-cytoplasimic localization at the different phase of cell cycle in cancer cells. By direct stochastic optical reconstruction microscopy imaging, we find that STAT3 forms various number and size of clusters at the different cell-cycle stage, which could not be clearly observed by conventional fluorescent microscopy. STAT3 clusters get more and larger gradually from G1 to G2 phase, during which time transcription and other related activities goes on consistently. The results suggest that there is an intimate relationship between the clustered characteristic of STAT3 and the cell-cycle behavior. Meanwhile, clustering would facilitate STAT3 rapid response to activating signals due to short distances between molecules. Our data might open a new door to develop an antitumor drug for inhibiting STAT3 signaling pathway by destroying its clusters.


[Infective endocarditis. A case report as mirror of the guidelines].
Even today, in times of modern antibiotic therapy, infective endocarditis is a disease with a high mortality which is difficult to diagnose and to treat. The changing clinical face of this disease in the last decades results from a changing predisposition of the patients, an increasing age, and is accompanied with shift from streptococci toward staphylococci as the main causative microorganisms. Evidence from randomized trials is limited due to a low incidence of the disease. Thus, application of the guidelines for diagnosis and treatment on a patient has always to respect the individual history, and the individual clinical course. The authors describe and comment the case of a patient with endocarditis of the native aortic valve due to S. epidermidis from diagnosis to discharge from the hospital following the current German guidelines for diagnosis and treatment of infective endocarditis.


Novel role of the small GTPase Rheb: its implication in endocytic pathway independent of the activation of mammalian target of rapamycin.
The Ras-homologous GTPase Rheb that is conserved from yeast to human appears to be involved not only in cell growth but also in nutrient uptake. Recent biochemical analysis revealed that tuberous sclerosis complex (TSC), a GTPase-activating protein (GAP), deactivates Rheb and that phosphatidylinositol 3'-kinase (PI3k)-Akt/PKB kinase pathway activates Rheb through inhibition of the GAP-mediated deactivation. Although mammalian target of rapamycin (mTOR) kinase is implicated in the downstream target of Rheb, the direct effector(s) and exact functions of Rheb have not been fully elucidated. Here we identified that Rheb expression in cultured cells induces the formation of large cytoplasmic vacuoles, which are characterized as late endocytic (late endosome- and lysosome-like) components. The vacuole formation required the GTP form of Rheb, but not the activation of the downstream mTOR kinase. These results suggest that Rheb regulates endocytic trafficking pathway independent of the previously identified mTOR pathway. The physiological roles of the two Rheb-dependent signaling pathways are discussed in terms of nutrient uptake and cell growth or cell cycle progression.


[Molecular basis of hyperammonemia secondary to asparaginase: from therapeutic efficacity to toxicity].
Asparaginase is a key molecule in the treatment of acute lymphoblastic leukemia. It has improved response rates to chemotherapy. However, this is not without consequences. Therapeutic efficacy is sometimes achieved at the expense of toxicities that can lead to treatment discontinuation. Among them, patients can develop hyperammonemia which can sometimes be symptomatic leading to neurological disorders that can go as far as hyperammonemic coma or even death. Through a review of the current state of the literature, the objective is to understand the disparity of ammonia values as well as the clinical heterogeneity for a given ammonia concentration. A review of the literature including more than eighty publications was performed. The glutaminase activity of asparaginase seems to play an important role in the development of hyperammonia. At present, no risk factors have been identified for the development of hyperammonemia. On the other hand, the question of the impact of pre-analysis phase arises. Indeed, asparaginase continues to exert its activity in vitro, which leads to an artefactual increase in ammonia.


Genome-Wide Probing of RNA Structures In Vitro Using Nucleases and Deep Sequencing.
RNA structure probing is an important technique that studies the secondary and tertiary conformations of an RNA. While it was traditionally performed on one RNA at a time, recent advances in deep sequencing has enabled the secondary structure mapping of thousands of RNAs simultaneously. Here, we describe the method Parallel Analysis for RNA Structures (PARS), which couples double and single strand specific nuclease probing to high throughput sequencing. Upon cloning of the cleavage sites into a cDNA library, deep sequencing and mapping of reads to the transcriptome, the position of paired and unpaired bases along cellular RNAs can be identified. PARS can be performed under diverse solution conditions and on different organismal RNAs to provide genome-wide RNA structural information. This information can also be further used to constrain computational predictions to provide better RNA structure models under different conditions.


Short-term and long-term effects on visual word recognition.
Effects of lexical and sublexical variables on visual word recognition are often treated as homogeneous across participants and stable over time. In this study, we examine the modulation of frequency, length, syllable and bigram frequency, orthographic neighborhood, and graphophonemic consistency effects by (a) individual differences, and (b) item repetition. A group of 129 participants performed lexical decision and naming, in counterbalanced order, using a set of 150 Greek words in which these variables were decorrelated. Frequency, length, and syllable frequency effects were reduced by a preceding task. Length effects were inversely related to years of education. Neighborhood effects depended on the metric used. There were no significant effects or interactions of bigram frequency or consistency. The results suggest that exposure to a word causes transient effects that may cumulatively develop into permanent individual differences. Models of word recognition must incorporate item-specific learning to account for these findings.


Disease Severity in Moderate-to-Severe COVID-19 Is Associated With Platelet Hyperreactivity and Innate Immune Activation.
Hemostasis and inflammation are both dysregulated in patients with moderate-to-severe coronavirus disease 2019 (COVID-19). Yet, both processes can also be disturbed in patients with other respiratory diseases, and the interactions between coagulation, inflammation, and disease severity specific to COVID-19 are still vague. Hospitalized patients with acute respiratory symptoms and with severe acute respiratory syndrome coronavirus 2 (SARS-CoV2)-positive (COVpos) and SARS-CoV2-negative (COVneg) status were included. We assessed adenosine diphosphate (ADP)-, thrombin receptor activator peptide 6 (TRAP)-, and arachidonic acid (AA)-induced platelet reactivity by impedance aggregometry, as well as leukocyte subtype spectrum and platelet-leukocyte aggregates by flow cytometry and inflammatory cytokines by cytometric bead array. ADP-, TRAP-, and AA-induced platelet reactivity was significantly higher in COVpos than in COVneg patients. Disease severity, assessed by sequential organ failure assessment (SOFA) score, was higher in COVpos than in COVneg patients and again higher in deceased COVpos patients than in surviving COVpos. The SOFA score correlated significantly with the mean platelet volume and TRAP-induced platelet aggregability. A larger percentage of classical and intermediate monocytes, and of CD4pos T cells (TH) aggregated with platelets in COVpos than in COVneg patients. Interleukin (IL)-1 receptor antagonist (RA) and IL-6 levels were higher in COVpos than in COVneg patients and again higher in deceased COVpos patients than in surviving COVpos. IL-1RA and IL-6 levels correlated with the SOFA score in COVpos but not in COVneg patients. In both respiratory disease groups, absolute levels of B-cell-platelet aggregates and NK-cell-platelet aggregates were correlated with ex vivo platelet aggegation upon stimulation with AA and ADP, respectively, indicating a universal, but not a COVID-19-specific mechanism. In moderate-to-severe COVID-19, but not in other respiratory diseases, disease severity was associated with platelet hyperreactivity and a typical inflammatory signature. In addition to a severe inflammatory response, platelet hyperreactivity associated to a worse clinical outcome in patients with COVID-19, pointing to the importance of antithrombotic therapy for reducing disease severity.


Aligning Practice Data and Institution-specific CPD: Medical Quality Management as the Driver for an eLearning Development Process.
For hospital physicians, alignment of Continuing Professional Development (CPD) with quality improvement efforts is often absent or rudimentary. The purpose of this study was to evaluate a CPD development process that created accessible learning opportunities and aligned CPD with practice data. We conducted a chart audit to identify patient safety and quality of care issues within the institution, then established an eLearning approach that supported quick and cost effective development of high-quality interactive CPD opportunities. We tested a pilot module on the management of common infections in sub-acute care settings with fifteen (68%) residents and three staff physicians to evaluate the approach. One resident and three staff agreed to a follow-up interview. The satisfaction survey indicated that participants felt the content was generally appropriate and the module well designed. Significant improvements to knowledge were reported in the multi-drug resistance (Mean Difference = 25%, p = 0.002), infection management (MD = 32%, p < 0.001), and cellulitis risk factor (MD = 22%, p = 0.02) questions, as well as in the overall score (MD = 19%, p < 0.001). In terms of confidence in their answers, the mean rating pre-module was 3.17, rising significantly to 3.92 post-module (p < 0.001). In this way, collaboration between quality management and education committees allowed for the development of relevant CPD for physicians, with eLearning providing a timely and accessible way to deliver training on emerging issues.


Experimental Determination of Activation Energies for Covalent Bond Formation via Ion/Ion Reactions and Competing Processes.
The combination of ion/ion chemistry with commercially available ion mobility/mass spectrometry systems has allowed rich structural information to be obtained for gaseous protein ions. Recently, the simple modification of such an instrument with an electrospray reagent source has allowed three-dimensional gas-phase interrogation of protein structures through covalent and noncovalent interactions coupled with collision cross section measurements. However, the energetics of these processes have not yet been studied quantitatively. In this work, previously developed Monte Carlo simulations of ion temperatures inside traveling wave ion guides are used to characterize the energetics of the transition state of activated ubiquitin cation/sulfo-benzoyl-HOAt reagent anion long-lived complexes formed via ion/ion reactions. The ΔH‡ and ΔS‡ of major processes observed from collisional activation of long-lived gas-phase ion/ion complexes, namely collision induced unfolding (CIU), covalent bond formation, or neutral loss of the anionic reagent via intramolecular proton transfer, were determined. Covalent bond formation via ion/ion complexes was found to be significantly lower energy compared to unfolding and bond cleavage. The ΔG‡ values of activation of all three processes lie between 55 and 75 kJ/mol, easily accessible with moderate collisional activation. Bond formation is favored over reagent loss at lower activation energies, whereas reagent loss becomes competitive at higher collision energies. Though the ΔG‡ values between CIU of a precursor ion and covalent bond formation of its ion/ion product complex are comparable, our data suggest covalent bond formation does not require extensive isomerization.


A Small GTPase, OsRab6a, is Involved in the Regulation of Iron Homeostasis in Rice.
Plants have evolved two distinct strategies to acquire iron (Fe) from soils. However, the regulatory mechanisms underlying the Fe acquisition remain largely elusive. There is emerging evidence that small GTPases are involved in the responses of plants to environmental cues. Here, we identified a gene encoding a small GTPase, OsRab6a, in rice and characterized its role in Fe acquisition by generating transgenic rice plants with overexpression and knockdown of OsRab6a OsRab6a shared conserved functional domains with other known members of the Rab subfamily and localized ubiquitously in the cytoplasm and nucleus. The expression of OsRab6a was rapidly and transiently up-regulated by Fe deficiency. No differences in growth and development among the OsRab6a-overexpression, OsRab6a-RNAi (RNA interference) and wild-type plants were detected when grown in Fe-sufficient medium. However, overexpression of OsRab6a in rice plants conferred greater tolerance to Fe deficiency than RNAi and wild-type plants, as evidenced by higher seedling height, and greater biomass, Chl contents and Fe concentrations in shoots, roots and grains in the overexpression lines than wild-type and RNAi plants. Moreover, the overexpression lines exhibited larger root systems than wild-type and RNAi plants in Fe-deficient medium. Exposure to Fe-deficient medium led to up-regulation of OsIRO2, OsIRT1, OsNAS1 and OsNAS2 in both wild-type and transgenic rice plants, with the magnitude of up-regulation positively correlated with the expression levels of OsRab6a These results may suggest that OsRab6a plays an important role in the regulation of Fe acquisition in rice plants by modulating physiological processes involved in Fe acquisition and root system architecture in response to Fe-deficient medium.


Kaposiform hemangioendothelioma: case report and literature review.
We report the identification of a kaposiform hemangioendothelioma (KH) in the oropharynx of a 3-year-old boy. This is a rare endothelial-derived spindle cell neoplasm affecting children and early adolescents with features common to capillary hemangioma and Kaposi sarcoma. Nine cases of head and neck KH have been reported, this being the first in the otolaryngology literature. Our patient underwent wide local excision and has remained tumor free for over 1 year. KH should be considered in the differential diagnosis of a vascular lesion demonstrating unexpected behavior from that of a hemangioma.


Vemurafenib- and Cobimetinib-Associated Drug Reaction With Eosinophilia and Systemic Symptoms in a Patient With Metastatic Melanoma.
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe hypersensitivity reaction associated with drug exposure. Recognizing signs of DRESS and stopping the offending agent is essential for proper treatment. In this case report, we present an interesting case of DRESS following the recent initiation of vemurafenib and cobimetinib for the treatment of metastatic melanoma in a patient who previously had been on pembrolizumab without adverse skin reactions. In this case report, we highlight the ambiguity of using the Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) scoring criteria in the hospital setting for recognizing DRESS in patients with toxic epidermal necrolysis (TEN)-type presentation of DRESS.


The genetic polymorphisms and colonization process of olive fly populations in Turkey.
The olive fruit fly, Bactrocera oleae, is the most important pest of olives in olive growing regions worldwide, especially in the Mediterranean basin and North America. Despite the economic importance of the olive fly, the colonization route of this species is unclear. We used nuclear microsatellite markers and mitochondrial DNA to provide information about the population structure and invasion route of olive fly populations in Turkey, as representative of the Eastern Mediterranean region. Adult fly samples were collected from 38 sublocations covering all olive growing regions in Turkey. The simple sequence variability data revealed a significant genetic variability in olive fly populations and a certain degree of differentiation between Mediterranean and Aegean populations. Mediterranean populations harbor higher levels of microsatellite variation than Aegean populations, which points to the eastern part of the Mediterranean as the putative source of invasion. mtDNA results suggest olive flies from the western part of Turkey are closely related to Italo-Aegean flies of the Mediterranean basin and the olive fly populations have invaded the northern part of the Mediterranean basin through western Turkey. In addition, finding specific American haplotypes in high frequencies might indicate that Turkey is the possible source of American olive fly populations. In order to more precisely characterize the population structure and invasion routes of this organism, more DNA-based sequence analysis should be carried out worldwide.


Community effectiveness of pyriproxyfen as a dengue vector control method: A systematic review.
Vector control is the only widely utilised method for primary prevention and control of dengue. The use of pyriproxyfen may be promising, and autodissemination approach may reach hard to reach breeding places. It offers a unique mode of action (juvenile hormone mimic) and as an additional tool for the management of insecticide resistance among Aedes vectors. However, evidence of efficacy and community effectiveness (CE) remains limited. The aim of this systematic review is to compile and analyse the existing literature for evidence on the CE of pyriproxyfen as a vector control method for reducing Ae. aegypti and Ae. albopictus populations and thereby human dengue transmission. Systematic search of PubMed, Embase, Lilacs, Cochrane library, WHOLIS, Web of Science, Google Scholar as well as reference lists of all identified studies. Removal of duplicates, screening of abstracts and assessment for eligibility of the remaining studies followed. Relevant data were extracted, and a quality assessment conducted. Results were classified into four main categories of how pyriproxyfen was applied: - 1) container treatment, 2) fumigation, 3) auto-dissemination or 4) combination treatments,-and analysed with a view to their public health implication. Out of 745 studies 17 studies were identified that fulfilled all eligibility criteria. The results show that pyriproxyfen can be effective in reducing the numbers of Aedes spp. immatures with different methods of application when targeting their main breeding sites. However, the combination of pyriproxyfen with a second product increases efficacy and/or persistence of the intervention and may also slow down the development of insecticide resistance. Open questions concern concentration and frequency of application in the various treatments. Area-wide ultra-low volume treatment with pyriproxyfen currently lacks evidence and cannot be recommended. Community participation and acceptance has not consistently been successful and needs to be further assessed. While all studies measured entomological endpoints, only two studies measured the reduction in human dengue cases, with inconclusive results. Although pyriproxyfen is highly effective in controlling the immature stages of dengue transmitting mosquitoes, and-to a smaller degree-adult mosquitoes, there is weak evidence for a reduction of human dengue cases. More well designed larger studies with appropriate standardised outcome measures are needed before pyriproxyfen is incorporated in routine vector control programmes. Additionally, resistance to pyriproxyfen has been reported and needs investigation.


Facile synthesis of multi-layer Co(OH)2/CeO2-g-C3N4 ternary synergistic heterostructure for efficient photocatalytic oxidation of NO under visible light.
In this work, we report a one-step synthesis of ternary Z-scheme Co(OH)2/CeO2-g-C3N4 (CoCe-CN) heterostructure via hydrothermal method. Owing to the modification of Co(OH)2 and CeO2, the existence of Co(OH)2 as an electron acceptor-donor center between CeO2 and g-C3N4 accelerates the electron transfer and provides extra OH- reaction pathway for photocatalytic oxidation of NO. As a result, 50CoCe-CN (Co and Ce accounting for 25% mass ratio separately) achieved a 53.5% conversion efficiency of NO at 600 ppb concentration, which is 1.82 times that of g-C3N4 under visible light. The results of the DFT analysis and element distribution of cobalt and ceria provide convincing evidence supporting the existence of a novel multi-layer structure in the CoCe-CN photocatalyst. This structure involves the loading of CeO2 and Co(OH)2 on the g-C3N4 surface, and Co(OH)2 as a co-catalyst introduced between CeO2 and g-C3N4 realizes the synergy between CeO2 and Co(OH)2 which further improve the photocatalytic properties. The higher photocatalytic efficiencies observed in the CoCe-CN photocatalysts compared to those containing only cobalt (Co-CN) or ceria (Ce-CN) provide further evidence of the synergistic effect of these two elements. This work demonstrates a more efficient and effective ternary photocatalytic system, with greater practical potential for photocatalytic oxidation of NO.


Estimation of time trends of incidence of prostate cancer--an Indian scenario.
With increase in life expectancy, adoption of newer lifestyles and screening using prostate specific antigen (PSA), the incidence of prostate cancer is on rise. Globally prostate cancer is the second most frequently diagnosed cancer and sixth leading cause of cancer death in men. The present communication makes an attempt to analyze the time trends in incidence for different age groups of the Indian population reported in different Indian registries using relative difference and regression approaches. The data published in Cancer Incidence in Five Continents for various Indian registries for different periods and/or publications by the individual registries served as the source materials. Trends were estimated by computing the mean annual percentage change (MAPC) in the incidence rates using the relative difference between two time periods (latest and oldest) and also by estimation of annual percentage change (EAPC) by the Poisson regression model. Age adjusted incidence rates (AAR) of prostate cancer for the period 2005-2008 ranged from 0.8 (Manipur state excluding Imphal west) to 10.9 (Delhi) per 105 person-years. Age specific incidence rates (ASIR) increased in all PBCRs especially after 55 years showing a peak incidence at +65 years clearly indicating that prostate cancer is a cancer of the elderly. MAPC in crude incidence rate(CR) ranged from 0.14 (Ahmedabad) to 8.6 (Chennai) . Chennai also recorded the highest MAPC of 5.66 in ASIR in the age group of 65+. Estimated annual percentage change (EAPC) in the AAR ranged from 0.8 to 5.8 among the three registries. Increase in trend was seen in the 5-64 year age group cohort in many registries and in the 35-44 age group in Metropolitan cities such as Delhi and Mumbai. Several Indian registries have revealed an increasing trend in the incidence of prostate cancer and the mean annual percentage change has ranged from 0.14-8.6.


Availability of Definitive Hospital Care for Children.
Timely and efficient access to hospital care is essential for the health and well-being of children. As insurance networks, accountable care organizations, and alternative payment methods evolve, these new systems of care must continue to serve the needs of children. To test the hypothesis that the availability of definitive pediatric hospital care is significantly more limited than adult care and is decreasing disproportionately. This study used case mix data during fiscal years 2004 through 2014 to measure transfer frequency and identify the site of care completion for all patients seen in acute care hospitals throughout Massachusetts. Patterns of care among children were then compared with patterns of care among adults. Participants were all patients seen in an emergency department or admitted to a hospital from 2004 through 2014, including more than 34 million encounters. Hospital Capability Index and Regionalization Index for all acute care hospitals and all conditions within the Clinical Classifications Software of the Healthcare Cost and Utilization Project. Over the study period, the Commonwealth of Massachusetts hospital system was composed of 66 acute care hospitals. After excluding newborns and mental health conditions, there were 34 511 312 encounters, with 25 226 014 emergency department visits and 9 285 298 observation or full admissions. From 2004 through 2014, care for adults and children concentrated among hospitals but much more so for pediatric care. The number of children requiring care in more than one hospital increased 36.2% (from 7190 to 9793). The median (interquartile range [IQR]) Hospital Capability Index, reflecting the likelihood of a hospital completing a patient's care without transfer, decreased 10.8% (from 0.74 [IQR, 0.65-0.81] to 0.66 [IQR, 0.53-0.76]) for adult care and 65.0% (0.20 [IQR, 0.05-0.34] to 0.07 [IQR, 0.01-0.23]) for pediatric care. Almost all of the shift was from nonacademic to academic hospitals. The median Regionalization Index, reflecting the degree to which care for specific conditions is regionalized, was very high for pediatric conditions and further increased from 0.79 (IQR, 0.67-0.91) to 0.87 (IQR, 0.80-0.91). Over the same decade, the mean Regionalization Index for adult conditions was low and increased modestly from 0.25 (IQR, 0.14-0.39) to 0.32 (IQR, 0.19-0.46). Among pediatric conditions, more than 75% were highly regionalized in 2014 compared with fewer than 50% in 2004. Pediatric hospital care has become increasingly concentrated, and many children with common conditions are now less frequently treated in the community. This finding has significant implications for systemwide capacity management and should be specifically accounted for in public health activities, disaster planning, and determinations of network adequacy.


Federal Employees Health Benefits Program: Removal of Eligible and Ineligible Individuals From Existing Enrollments. Final rule.
The United States Office of Personnel Management (OPM) is issuing a final rule amending Federal Employees Health Benefits (FEHB) Program regulations to provide a process for removal of certain identified individuals who are found not to be eligible as family members from FEHB enrollments. This process would apply to individuals for whom there is a failure to provide adequate documentation of eligibility when requested. This action also amends Federal Employees Health Benefits (FEHB) Program regulations to allow certain eligible family members to be removed from existing self and family or self plus one enrollments.


A mitochondrial checkpoint to adaptive anticancer immunity.
BCL2 robustly preserves mitochondrial integrity, hence inhibiting innate immune signaling and apoptotic cell death in several cell types. Here, we comment on our recent data demonstrating that BCL2 also limits the ability of dendritic cells to elicit adaptive immune responses, lending support to a universal immunosuppressive function for the mitochondrial immune checkpoint.


Subversion of host recognition and defense systems by Francisella spp.
Francisella tularensis is a gram-negative intracellular pathogen and the causative agent of the disease tularemia. Inhalation of as few as 10 bacteria is sufficient to cause severe disease, making F. tularensis one of the most highly virulent bacterial pathogens. The initial stage of infection is characterized by the "silent" replication of bacteria in the absence of a significant inflammatory response. Francisella achieves this difficult task using several strategies: (i) strong integrity of the bacterial surface to resist host killing mechanisms and the release of inflammatory bacterial components (pathogen-associated molecular patterns [PAMPs]), (ii) modification of PAMPs to prevent activation of inflammatory pathways, and (iii) active modulation of the host response by escaping the phagosome and directly suppressing inflammatory pathways. We review the specific mechanisms by which Francisella achieves these goals to subvert host defenses and promote pathogenesis, highlighting as-yet-unanswered questions and important areas for future study.


Musculoskeletal disorders caused by gas cylinder handling tasks: A case study report.
This case study used the Nordic Musculoskeletal Questionnaire (NMQ) to explore work that involves handling gas cylinders and to determine risk factors that may cause related injuries. The NMQ survey was distributed to 100 gas cylinder handlers in Taiwan, and their handling tasks were analyzed. The results showed that the overall prevalence of musculoskeletal disorders was 91% within 1 year. More than half of the respondents (62%) experienced shoulder discomfort, followed by lower back/waist (57%) and neck (47%) discomfort. Daily work hours (>10 h) were primary factors influencing the development of discomfort when handling gas cylinders, whereas the daily delivery frequency (>30 deliveries) was relevant to the prevalence of lower limb discomfort. Individual factors also substantially influenced upper body, lower back/waist, and knee discomfort (i.e., age, job tenure, and exercise). The findings of this study can serve as references in the prevention of work-related musculoskeletal disorders caused by performing gas cylinder handling tasks.


Incorporating real time velocity map image reconstruction into closed-loop coherent control.
We report techniques developed to utilize three-dimensional momentum information as feedback in adaptive femtosecond control of molecular dynamics. Velocity map imaging is used to obtain the three-dimensional momentum map of the dissociating ions following interaction with a shaped intense ultrafast laser pulse. In order to recover robust feedback information, however, the two-dimensional momentum projection from the detector must be inverted to reconstruct the full three-dimensional momentum of the photofragments. These methods are typically slow or require manual inputs and are therefore accomplished offline after the images have been obtained. Using an algorithm based upon an "onion-peeling" (also known as "back projection") method, we are able to invert 1040 × 1054 pixel images in under 1 s. This rapid inversion allows the full photofragment momentum to be used as feedback in a closed-loop adaptive control scheme, in which a genetic algorithm tailors an ultrafast laser pulse to optimize a specific outcome. Examples of three-dimensional velocity map image based control applied to strong-field dissociation of CO and O2 are presented.


Stopping Manual and Vocal Actions in Tourette's Syndrome.
Evidence that Tourette's syndrome (TS) disrupts inhibitory motor control is highly mixed. The authors investigated inhibitory control of manual and vocal actions in young adults with relatively uncomplicated, persistent TS. Both TS and control groups showed similar response latencies when executing manual and vocal reactions, but individuals with TS were slower at stopping their manual and vocal responses. While alterations in inhibitory motor control may not be a generalizable phenomenon in TS, these results add to an emerging literature suggesting that individuals with relatively uncomplicated TS, whose symptoms persist into adulthood, show disruption to inhibitory control mechanisms.


Molecular docking and simulation studies of flavonoid compounds against PBP-2a of methicillin-resistant Staphylococcus aureus.
Methicillin-Resistant Staphylococcus aureus (MRSA), a pathogenic bacterium that causes life-threatening outbreaks such as community-onset and nosocomial infections as emerging 'superbug'. Time and motion study of its virulent property developed resistance against most of the antibiotics such as Vancomycin. Thereby, to curb this problem entails the development of new therapeutic agents. Plant-derived antimicrobial agents have recently piqued people's interest, so in this research, 186 flavonoids compound selected to unmask the best candidates that can act as potent inhibitors against the Penicillin Binding Protein-2a (PBP-2a) of MRSA. Molecular docking performed using PyRx and GOLD suite to determine the binding affinities and interactions between the phytochemicals and the PBP-2a. The selected candidates strongly interact with the different amino acid residues. The 30 ns molecular dynamics (MD) simulations with five top-ranked compounds such as Naringin, Hesperidin, Neohesperidin, Didymin and Icariin validated the docking interactions. These findings are also strongly supported by root-mean-square deviation, root-mean-square fluctuation and the radius of gyration. ADME/T analysis demonstrates that these candidates appear to be safer inhibitors. Our findings point to natural flavonoids as a promising and readily available source of adjuvant antimicrobial therapy against resistant strains in the future.Communicated by Ramaswamy H. Sarma.


Rectal red blood loss in a healthy toddler is not always a juvenile polyp.
Aim Heterotopic gastric mucosa is a well-known congenital anomaly in Meckel's diverticula and duplication cysts. Solitary heterotopic gastric mucosa in the rectum is a rare and frequently overlooked abnormality. Starting from a patient history, the literature is searched and all cases reported over the past 20 years are reviewed and compared to a summary of the older cases. Differences between adult and childhood presentation are outlined and our patient is compared with prior reported cases. Case A 3-year-old girl presented with recurrent rectal blood loss caused by heterotopic gastric mucosa without duplication cyst. She was endoscopically treated with two-stage endoscopic surgical dissection (ESD). Up to now, rectal heterotopic gastric mucosa has been reported in 34 adults and 24 children, including this patient. There is an overall male dominance (69%). Presenting complaints in children were recurrent fresh blood loss per anum (96%), pain (46%), perineal ulcers (25%), diarrhoea (8%) and one patient had an ano-cutaneous fistula. Endoscopy revealed a mucosal elevation with a slightly different aspect (33%), a polyp (42%) and a solitary ulcer (25%). Endoscopy in adults reveals more frequently polyps compared to children. Treatment in childhood is mainly surgical where adults are more frequently treated with endoscopic techniques. Conclusion In a child with recurrent rectal bleeding in good general health, it is important to withhold heterotopic gastric mucosa in the differential diagnosis and take sufficient biopsies during endoscopy.


Low-noise and high-speed photodetection system using optical feedback with a current amplification function.
A photodetection system with an optical-feedback circuit accompanied by current amplification was fabricated to minimize the drawbacks associated with a transimpedance amplifier (TIA) with a very high resistance feedback resistor. Current amplification was implemented by extracting an output light from the same light source that emitted the feedback light. The current gain corresponds to the ratio of the photocurrent created by the output light to that created by the feedback light because the feedback current value is identical to the input photocurrent value generated by an input light to be measured. The current gain has no theoretical limit. The output light was detected by a photodiode with a TIA having a small feedback resistance. The expression for the input-referred noise current of the optical-feedback photodetection system was derived, and the trade-off between sensitivity and response, which is a characteristic of TIA, was found to considerably improve. An optical-feedback photodetection system with an InGaAs pin photodiode was fabricated. The measured noise equivalent power of the system was 1.7 fW/Hz(1/2) at 10 Hz and 1.3 μm, which is consistent with the derived expression. The time response of the system was found to deteriorate with decreasing photocurrent. The 50% rise time for a light pulse input increased from 3.1 μs at a photocurrent of 10 nA to 15 μs at photocurrents below 10 pA. The bandwidth of the input-referred noise current was 7 kHz, which is consistent with rise times below 10 pA.


Low-grade proteinuria and microalbuminuria in renal transplantation.
Nephrotic-range proteinuria has been known for years to be associated with poor renal outcome. Newer evidence indicates that early (1-3 months after transplantation) low-grade proteinuria and microalbuminuria (1) provide information on the graft in terms of donor characteristics and ischemia/reperfusion injury, (2) may occur before the development of donor-specific antibodies, (3) predict the development of diabetes and cardiovascular events, and (4) are associated with reduced long-term graft and patient survivals. Low-grade proteinuria and microalbuminuria are also predictive of diabetes, cardiovascular morbidity, and death in nontransplanted populations, which may help us to understand the pathophysiology of low-grade proteinuria or microalbuminuria in renal transplantation. The impact of immunosuppressive medications, including mammalian target of rapamycin inhibitors, on graft survival is still discussed, and the effect on proteinuria is crucial to the debate. The fact that chronic allograft rejection may exist as early as 3 months after renal transplantation indicates that optimal management of low-grade proteinuria or microalbuminuria should occur very early after transplantation to improve long-term renal function and the overall outcome of renal transplant recipients. The presence of low-grade proteinuria or microalbuminuria early after transplantation must be taken into account to choose adequate immunosuppressive and antihypertensive medications. Limited information exists regarding the benefit of therapeutic interventions to reduce low-grade proteinuria or microalbuminuria. Whether renin angiotensin blockade results in optimal nephroprotection in patients with low-grade proteinuria or microalbuminuria is not proven, especially in the absence of chronic allograft nephropathy. Observational studies and randomized clinical trials yield conflicting results. Finally, randomized clinical trials are urgently needed.


BCG-unresponsive non-muscle-invasive bladder cancer: recommendations from the IBCG.
Intravesical immunotherapy with live attenuated BCG remains the standard of care for patients with high-risk and intermediate-risk non-muscle-invasive bladder cancer (NMIBC). Most patients initially respond, but recurrence is frequent and progression to invasive cancer is a concern. No established and effective intravesical therapies are available for patients whose tumours recur after BCG, representing a clinically important unmet need. Development and discovery of treatment options for BCG-unresponsive NMIBC is a high priority in order to decrease the morbidity, burden of health-care expenditures, and mortality related to bladder cancer. This Review of treatment options after BCG failure focuses on principles of optimal management emerging therapies, thus enabling a synthesis of recommendations for management for such patients.


[Transient ischemic dilatation of the left ventricle observed on dipyridamole-stressed thallium-201 scintigraphy].
To assess clinical significance of transient ischemic dilatation of the left ventricle (TID) on dipyridamole-stressed 201Tl myocardial scintigraphy, 110 patients suspected with coronary artery disease, including 13 with normal coronary, 48 with single vessel disease, 30 with 2 vessel disease, and 19 with 3 vessel disease were analyzed. TID was visually and quantitatively assessed calculating the ratio of the area within the left ventricular region on the initial and delayed image (TID ratio). TID was observed in 3 of 1 vessel disease (6%), 5 of 2 vessel disease (17%), and 8 of 3 vessel disease (42%). None of normal coronary artery showed TID. In patients with multivessel disease (MVD), TID was observed more frequently (27%) than in patients with 1 vessel disease (6%) (p < 0.025). Furthermore, the TID ratio tended to be higher (1.15 +/- 0.11) than those with single vessel disease (1.03 +/- 0.03). To identify patients with MVD, TID had a sensitivity of 27% and a specificity of 95%. ECG changes were observed more often in patients with TID than those without TID. Five patients showing TID underwent coronary artery bypass graft surgery, TID disappeared postoperatively in each patient. In conclusion, TID on dipyridamole 201Tl scan seems to be a specific although not sensitive marker for detecting MVD.


[The localization and differential diagnosis of benign and malignant gynaecological tumours in the axial computer assisted tomogram (author's transl)].
40 computer assisted tomographies of the vagina, the uterus and the ovaries were evaluated. The differential diagnosis between malignant and benign neoplasms is difficult unless there is spread into the soft tissues. The early diagnosis of ovarian neoplasms by axial computer assisted tomography is impossible. We are of the opinion that axial computer assisted tomography should be performed as early as possible in the diagnosis of local recurrences of malignant tumours of the female genital tract.


COVID-19: Present and Future Challenges for Dental Practice.
COVID-19 was declared a pandemic by the World Health Organization, with a high fatality rate that may reach 8%. The disease is caused by SARS-CoV-2 which is one of the coronaviruses. Realizing the severity of outcomes associated with this disease and its high rate of transmission, dentists were instructed by regulatory authorities, such as the American Dental Association, to stop providing treatment to dental patients except those who have emergency complaints. This was mainly for protection of dental healthcare personnel, their families, contacts, and their patients from the transmission of virus, and also to preserve the much-needed supplies of personal protective equipment (PPE). Dentists at all times should competently follow cross-infection control protocols, but particularly during this critical time, they should do their best to decide on the emergency cases that are indicated for dental treatment. Dentists should also be updated on how this pandemic is related to their profession in order to be well oriented and prepared. This overview will address several issues concerned with the COVID-19 pandemic that directly relate to dental practice in terms of prevention, treatment, and orofacial clinical manifestations.


Gender Disparities in the Food Insecurity-Overweight and Food Insecurity-Obesity Paradox among Low-Income Older Adults.
Obesity and obesity-related comorbidities are increasing among older adults. Food insecurity is a nutrition-related factor that coexists with obesity among low-income individuals. The majority of the research on the food insecurity-obesity paradox has been conducted on low-income mothers and children, with research lacking on large diverse samples of older adults. The purpose of this study was to assess gender disparities in the association between food insecurity and overweight and obesity among low-income older adults. Cross-sectional 2011 and 2012 National Health Interview Survey data were used. Food insecurity status was determined by ≥3 affirmative responses on the 10-item US Department of Agriculture Food Security Scale (FSS). Body mass index (BMI) was calculated as outlined by the Centers for Disease Control and Prevention based on self-reported height and weight. Adults included were low-income (≤1.99 federal poverty level [FPL]), older (aged ≥60 years), with a normal BMI (18.5) or greater who had complete data on FSS, BMI, and the following covariates: age, race or ethnicity, marital status, income, nativity status, physical activity, poor health status, health insurance coverage, problems paying medical bills or for medicine, and region of residency (N=5,506). Multivariate logistic regression models were stratified by gender to estimate the association between food insecurity and higher weight status. All models included covariates. In covariate-adjusted models, compared with low-income, food secure men, low-income, food-insecure men had 42% and 41% lower odds of being overweight and overweight or obese, respectively. Despite the high prevalence rate of obesity among low-income, food-insecure women, food insecurity was not significantly related to overweight, obesity, or overweight or obesity for older adult women in adjusted models. Food insecurity-overweight and -obesity paradox appears not to be present in older men. However, food insecurity and obesity coexist among low-income, older women.


The (un)dress of the mad poor in England, c.1650-1850. Part 2.
The second part of this paper assesses how far the dominant imagery of the (un)dress of the mad poor, found in the literary, medical and representational sources discussed in Part 1, corresponds with actual conditions and provisions for the poor insane as revealed in institutional and documentary sources. This is necessarily attempted through a selective sample of sources, in particular clothing procurement for the poor insane as chronicled in parochial records. More especially, the documentary accuracy of prevailing cultural representations is assessed through a case study of the records of Bethlehem (or 'Bedlam'/Bethlem) Hospital, the archetypal English madhouse.


Experimental evaluation of Pentas lanceolata flowers for wound healing activity in rats.
The ethanolic extract of the flowers of Pentas lanceolata given by oral route to rats at dose of 150 mg kg(-1) day(-1) for 10 days, was studied for its effect on wound healing, using excision wound mode. Significant increase in granulation tissue weight, tensile strength, hydroxyproline and glycosaminoglycan content was observed. Moderate increase in protein content was seen. There was significant reduction in the wound area measurement of the test group as compared to that of controls. The efficacious prohealing action may be due to increased collagen deposition as well as better alignment and maturation.


Self-assembly of porphyrin on graphene oxide in aqueous medium: fabrication, characterization, and photocatalytic studies.
We herein report the supramolecular self-assembly of a water soluble porphyrin, namely, 5,10,15,20-tetrakis(1-methyl-4-pyridinio)porphyrin-tetra(p-toluenesulfonate) (TMPyP), on the surface of graphene oxide (GO). The fabricated GO nanosheet and GO@TMPyP hybrid material composite have been characterized by using various spectroscopic and analytical techniques, e.g., scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM), and Fourier transform infrared (FT-IR) spectroscopy. The steady state absorption measurements of the GO@TMPyP self-assembly showed a significant red shift (∼20 nm) compared to those of the control TMPyP in water. The steady state fluorescence measurements showed a significant fluorescence quenching of the singlet excited state of TMPyP in the presence of GO. These findings suggest the electron transfer reaction from TMPyP to GO. The time resolved fluorescence measurements showed a considerable decrease in the lifetime of the singlet state of TMPyP in the presence of GO, from which the rate and efficiency of the electron transfers from TMPyP to GO were determined to be 1.93 × 109 s-1 and 91%, respectively. The transient absorption measurements showed a considerable quenching of the triplet excited state of TMPyP in the self-assembly. All these findings confirm the occurrence of efficient electronic interactions between TMPyP and GO in both the ground and excited states. In addition, the fabricated GO@TMPyP showed high photocatalytic activity for the degradation of methylene blue (MB) and methyl orange (MO) mixed dye pollutants in water under visible light irradiation.


The Utility of PET/CT in Guiding Radiotherapy Reduction for Children With Hodgkin Lymphoma Treated With ABVD.
ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) is standard upfront chemotherapy for adults diagnosed with Hodgkin lymphoma (HL), but positron emission tomography (PET)-based response data following ABVD is lacking for pediatrics. Among children who received ABVD for HL, we document interim and end of therapy PET-computed tomography (CT) response by Deauville criteria, and survival outcomes following a response-based reduction in involved field radiotherapy (IFRT). Children 18 years of age or below with HL treated with ABVD between 2006 and 2015 who had interim PET/CT scans after 2 cycles of chemotherapy were included. Interim and end of therapy PET/CT scans were retrospectively re-evaluated using Deauville criteria by 3 radiologists. Among 45 children, 32 (71%) met criteria for intermediate risk, 86% achieved rapid early response (RER) and only 4 (9%) received upfront IFRT. Patients achieving RER had superior 5-year event-free survival (EFS) 95%±4% versus 50%±18% (P≤0.001) and overall survival (OS) 100% versus 83%±15% (P=0.025). Patients with bulk who achieved RER and received no IFRT achieved 5-year EFS of 92%±6% and OS 100%. Low, intermediate, and high risk patients had 5-year EFS of 100%, 94%±4%, and 50%±18% (P=0.002) and 5-year OS of 100%, 100%, and 75%±15% (P=0.03). RER following 2 cycles of ABVD is predictive of survival outcomes in children and adolescents with HL and may identify a group who may omit IFRT.


Varicella-zoster virus myelitis: an expanding spectrum.
We report four cases of varicella-zoster virus (VZV)-associated myelopathy in adults. Myelopathy was remitting-exacerbating in two remarkable instances, once acute and once chronic. VZV myelopathy was diagnosed based on the close temporal relationship between rash and onset of myelopathy, and for the first time, by polymerase chain reaction, which revealed VZV DNA in the cerebral spinal fluid of three patients with pleocytosis weeks to months later. Magnetic resonance imaging was abnormal in three of four patients. Although all four patients were treated at some time with intravenous acyclovir, concomitant treatment with steroids and the presence of acquired immunodeficiency syndrome in one patient prevented conclusions about a favorable response to therapy. Myelopathy after VZV infection may be remitting-exacerbating in addition to acute or chronic. Detection of VZV DNA in cerebral spinal fluid months after rash was useful for diagnosis and suggests a role for virus in the pathogenesis of myelopathy.


Do multiple ionic interactions contribute to skeletal muscle fatigue?
During intense exercise or electrical stimulation of skeletal muscle the concentrations of several ions change simultaneously in interstitial, transverse tubular and intracellular compartments. Consequently the functional effects of multiple ionic changes need to be considered together. A diminished transsarcolemmal K(+) gradient per se can reduce maximal force in non-fatigued muscle suggesting that K(+) causes fatigue. However, this effect requires extremely large, although physiological, K(+) shifts. In contrast, moderate elevations of extracellular [K(+)] ([K(+)](o)) potentiate submaximal contractions, enhance local blood flow and influence afferent feedback to assist exercise performance. Changed transsarcolemmal Na(+), Ca(2+), Cl(-) and H(+) gradients are insufficient by themselves to cause much fatigue but each ion can interact with K(+) effects. Lowered Na(+), Ca(2+) and Cl(-) gradients further impair force by modulating the peak tetanic force-[K(+)](o) and peak tetanic force-resting membrane potential relationships. In contrast, raised [Ca(2+)](o), acidosis and reduced Cl(-) conductance during late fatigue provide resistance against K(+)-induced force depression. The detrimental effects of K(+) are exacerbated by metabolic changes such as lowered [ATP](i), depleted carbohydrate, and possibly reactive oxygen species. We hypothesize that during high-intensity exercise a rundown of the transsarcolemmal K(+) gradient is the dominant cellular process around which interactions with other ions and metabolites occur, thereby contributing to fatigue.


Compliance and persistence with treatment with parathyroid hormone for osteoporosis. A Danish national register-based cohort study.
Medical intervention is important in the treatment of osteoporosis, and compliance with medical treatment is essential for an optimal outcome. Based on Danish national registers, we found that compliance with parathyroid hormone (PTH) treatment is high and associated with marital status, working status, and type of PTH treatment. Compliance and persistence are essential for an optimal outcome during medical treatment of osteoporosis. We aimed to evaluate compliance and persistence with treatment with PTH in daily clinical practice in Danish patients and to describe factors affecting compliance. Register-based nationwide cohort study on all patients in Denmark initiates PTH or analogue treatment for osteoporosis in 2003-2010 (n = 4281). PTH drugs included were the PTH analogue teriparatide(1-34) and recombinant human PTH (rhPTH(1-84)). Compliance with treatment was calculated by using medication possession ratio (MPR). In the study period, 3702 patients were exclusively treated with teriparatide and 579 were exclusively treated with rhPTH(1-84). We found that for patients persistent with therapy for at least 18 months and with MPR >0.8, 83 % of the patients in the teriparatide group were compliant versus 72 % in the recombinant PTH group (p < 0.01). Being married/cohabiting, still in the labor market, and taking teriparatide were significantly associated with higher compliance, whereas age, gender, level of education, income, alcoholism, and Charlson comorbidity index were not associated with compliance. Compliance with PTH treatment overall is high, with teriparatide compliance higher than rhPTH(1-84), in patients persistent to therapy for 18 months. Compliance is associated with marital status, working status, and type of PTH treatment.


Qualitative evaluation of regioselectivity in the formation of di- and tri-6-O-tritylates of α-cyclodextrin.
The quantitative analysis of reaction products showed that the reaction of 6(A),6(D)-di-O-trityl-α-cyclodextrin (CD), AD-isomer, with trityl chloride in pyridine at 55 °C gave 6(A),6(B),6(E)-tri-O-trityl-α-CD, the amount of which was only 25% of that of simultaneously formed 6(A),6(B),6(D)-tri-O-trityl-α-CD. This indicates that the bulky trityl groups of glucopyranose-A and -D (Glu-A and -D, respectively) in the AD-isomer mainly retard the additional tritylation of the C(6)-OH of the adjacent glucopyranoses in a counter-clockwise direction (Glu-F and -C, respectively). (1)H NMR spectra of the AD-isomer showed that the O(6)-H and C(6)-H signals of Glu-C and -F are shifted upfield due to the ring current of the trityl groups. Thus, it is concluded that the bulky trityl groups on Glu-A and Glu-D are oriented to Glu-F and Glu-C, respectively, and sterically retard additional tritylation on Glu-F and Glu-C. Similar steric hindrance was also observed in the additional tritylations of mono-6-O-trityl-α-CD, 6(A),6(B)-di- and 6(A),6(C)-di-O-trityl-α-CD's.


Microwave-Assisted Syntheses of Rhodamine, Rhodol, and Fluorescein Derivatives.
A series of rhodol-; fluorescein- and rhodamines-based spirolactam compounds, bearing electron donor amines have been prepared. For this purpose we have redesigned the synthesis of the rhodol scaffold using 2-(2,4-dihydroxybenzoyl)benzoic acid obtaining one example rhodol methyl ester in good yields (25-30 %) Thus, one set of non-cytotoxic rhodamine-based compounds has been prepared using thermal and microwave assisted synthesis (40-78 %) and tested as high affinity ATP chemo-sensors.


Monoaxial distraction of ulna to second metacarpal followed by single bone forearm in massive post infective radial bone loss.
Radial bone loss associated with gross manus valgus deformity can be managed by open reduction internal fixation using intervening strut bone graft, callus distraction using ring or monoaxial fixator, and achieving union by distraction histogenesis. These methods are particularly suitable when bone loss is small. Single or staged procedure is described for congenital as well as in acquired extensive bone loss of radius. Distraction through radial proximal to distal segments, to achieve reduction of distal radio-ulnar joint (DRUJ), is also described in acquired cases. In the present series, functional results of distraction through ulna to 2(nd) metacarpal is studied alongwith, functional status of hand, stability of wrist, level of patient's satisfaction are also studied. 7 unilateral cases of radial loss (M = 5, F = 2) affecting 4 right hands of mean age 17 years (range 9 to 24 years) were included in this study. They were treated by distracting through ulna to 2(nd) metacarpal to achieve DRUJ alignment in first stage. Subsequently ulna was osteotomised and translated to distal stump of radius. It was then fixed to the distal radial remnant in 30° pronation in dominant and 30° supination non dominant hands. Union was achieved in all cases associated with beneficial cross union of distal ulna. Hand functions improved near to normal, with fully corrected stable wrist joint, hypertrophied ulna and without recurrence. All of them had practically complete loss of forearm rotations, however patients were fully satisfied. This method is particularly suitable when associated with 6 cm or more radial bone loss. But when loss is small, sacrifice of one bone may not be justifiable.